Biomechanical/Molecular Mechanisms in Alveolar Bone

牙槽骨的生物力学/分子机制

• 批准号: 7048381
• 负责人: TRACY E POPOWICS
• 金额: $ 13.5万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-06 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7048381
• 关键词: biomechanics; bone density; bone development; computed axial tomography; dental alveolus; dental development; dental occlusion; dental visualization; elasticity; gene expression; jaw; mechanical stress; molecular biology; nuclear factor kappa beta; osteoblasts; osteoclast activating factor; osteoclasts; osteoprotegerin; periodontium; physiologic bone resorption; protein localization; swine; tooth; tooth root; biomechanics; bone density; bone development; computed axial tomography; dental alveolus; dental development; dental occlusion; dental visualization; elasticity; gene expression; jaw; mechanical stress; molecular biology; nuclear factor kappa beta; osteoblasts; osteoclast activating factor; osteoclasts; osteoprotegerin; periodontium; physiologic bone resorption; protein localization; swine; tooth; tooth root

DESCRIPTION (provided by applicant): The long-term goal of this research is the identification of how tooth loading directs development of radicular alveolar bone, as the tooth erupts into function. The principal investigator, Dr. Tracy Popowics, is an assistant professor at the University of Washington School of Dentistry where the research will be conducted. The university offers an excellent environment for research, including both medical and dental schools that consistently rank among the top in the nation in terms of federal research support. The proposed research will develop Dr. Popowics's research career by 1) expanding the scope of her investigations into the development and function of mineralized tissue to include bone, and 2) acquiring the necessary skills to pursue molecular biology research. The proposed research tests the hypotheses that the expression of RANKL, RANK, and OPG molecules within the developing alveolar bone regulates the transition in alveolar bone from modeling during tooth eruption to remodeling during occlusal function, and that post-eruptive tooth loads provide the mechanism for shifts in osteoblast expression of RANKL in cancellous alveolar bone. In Specific Aim 1, the structural and biomechanical properties of alveolar bone will be measured at different developmental stages. These data will test the hypothesis that bone increases in mass, stiffness and strength throughout development, but that osseous tooth support increases in anisotropy only with tooth loading. Specific Aim 2 uses molecular methodologies to localize the expression of RANKL, RANK, OPG, and CSF-1 in periodontal tissues, and test the hypothesis that mechanical loads increase the osteoblast expression of RANKL, thus promoting osteoclastogenesis in cancellous alveolar bone. In Specific Aim 3, the effects of tooth loading on the growth and remodeling of alveolar bone will be tested through removing tooth loads from erupting M1's. Alveolar bone apposition and turnover and RANKL, RANK, OPG expression will be compared in control bone vs. these experimental conditions. Taken together, these studies will provide fundamental new information about how tooth loading modifies alveolar bone in newly erupted teeth and promotes adaptive tooth support.

描述（由申请人提供）：这项研究的长期目标是识别牙齿负荷如何指导牙齿牙槽骨的发展，因为牙齿爆发到功能中。首席研究员Tracy Popowics博士是华盛顿大学牙科学院的助理教授，将在那里进行研究。该大学为研究提供了一个绝佳的研究环境，包括在联邦研究支持方面始终如一地排名全国佼佼者的医学和牙科学校。拟议的研究将通过1）扩大对矿化组织的发展和功能的研究范围来发展Popowics博士的研究职业，包括骨骼，以及2）获得从事分子生物学研究的必要技能。提出的研究检验了一种假设，即发育中的肺泡骨内的RANKL，等级和OPG分子的表达调节牙槽骨在牙齿爆发期间的建模到咬合功能期间的重塑，而后牙齿后牙齿载荷为骨状骨骼表达的骨骼偏移的机制提供了骨骼骨骼的移位机制。在特定的目标1中，肺泡骨的结构和生物力学特性将在不同的发育阶段进行测量。这些数据将检验以下假设：骨骼在整个发育过程中的质量，刚度和强度增加，但是骨牙齿的支撑只有随着牙齿的负荷而增加。特定目标2使用分子方法论在牙周组织中定位RANKL，RANK，OPG和CSF-1的表达，并检验了机械载荷会增加RANKL的成骨表达的假说，从而促进了在纤维化骨骼中的破骨碎屑。在特定的目标3中，将通过从爆发的M1中去除牙齿负荷来测试牙齿负荷对牙槽骨生长和重塑的影响。牙槽骨的骨骼和周转率和RANKL，等级，OPG表达将在对照骨与这些实验条件中进行比较。综上所述，这些研究将提供有关牙齿荷载如何改变牙齿中牙齿骨骼的基本新信息，并促进自适应牙齿的支撑。